Engineering Modular DNA Reaction Networks for Signal Processing.

Diversified molecular information-processing methods have significant implications for nanoscale manipulation and control, monitoring and disease diagnosis of organisms, and direct intervention in biological activities. However, as an effective approach for implementing multifunctional molecular information processing, DNA reaction networks (DRNs) with numerous functionally specialized molecular structures have challenged them on scale and modular design, leading to increased network complexity, further causing problems such as signal leakage, attenuation, and cross-talk in network reactions. Our study developed a strategy for performing various signal-processing tasks through engineering modular DRNs composed of simple molecular structures. This strategy is based on a universal core unit with signal selection capability, and a timeadjustable signal self-resetting module is achieved by combing the core unit and self-resetting unit, which improves the time controllability of modular DRNs. In addition, multi-input and -output signal crosscatalytic and continuously adjustable signal delay modules were realized by combining core and threshold units, providing a flexible, precise method for modular DRNs to process the signal. The strategy simplifies the design of DRNs, helps generate design ideas for largescale integrated DRNs with multiple functions, and provides prospects in biocomputing, gene regulation, and biosensing.

Substantially reducing global PM2.5-related deaths under SDG3.9 requires better air pollution control and healthcare.

The United Nations' Sustainable Development Goal (SDG) 3.9 calls for a substantial reduction in deaths attributable to PM2.5 pollution (DAPP). However, DAPP projections vary greatly and the likelihood of meeting SDG3.9 depends on complex interactions among environmental, socio-economic, and healthcare parameters. We project potential future trends in global DAPP considering the joint effects of each driver (PM2.5 concentration, death rate of diseases, population size, and age structure) and assess the likelihood of achieving SDG3.9 under the Shared Socioeconomic Pathways (SSPs) as quantified by the Scenario Model Intercomparison Project (ScenarioMIP) framework with simulated PM2.5 concentrations from 11 models. We find that a substantial reduction in DAPP would not be achieved under all but the most optimistic scenario settings. Even the development aligned with the Sustainability scenario (SSP1-2.6), in which DAPP was reduced by 19%, still falls just short of achieving a substantial (≥20%) reduction by 2030. Meeting SDG3.9 calls for additional efforts in air pollution control and healthcare to more aggressively reduce DAPP.

Bubble DNA tweezer: A triple-conformation sensor responsive to concentration-ratios.

DNA tweezers, with their elegant simplicity and flexibility, have been pivotal in biosensing and DNA computing. However, conventional tweezers are confined to a binary transformation pre/post target signal recognition, limiting them to presence/absence judgments. This study introduces bubble DNA tweezers (BDT), capable of three distinct conformations based on variable target signal ratios. In contrast to traditional compact tweezers, BDT features a looser structure centered around a non-complementary bubble domain located between the tweezer arms' connecting axis and target signal recognition jaws. This bubble triggers toehold-free DNA strand displacement, leading to three conformational changes at different target signal concentrations. BDT detects presence/absence and true concentration with remarkable specificity and sensitivity. This adaptability is not confined to ideal scenarios, proving valuable in complex, noisy environments. Our method facilitates target DNA/miRNA signal quantification within a specific length range, promising applications in clinical research and environmental detection, while inspiring future biological assay innovations.

Surface oxygen concentration on the Qinghai-Tibet Plateau (2017-2022).

For the ecologically vulnerable Qinghai-Tibet Plateau (QTP), hypoxia is increasingly becoming an extremely important environmental risk factor that significantly affects the health of both humans and livestock in the plateau region, as well as hindering high-quality development. To focus on the problem of hypoxia, it is especially urgent to study the surface oxygen concentration (i.e., oxygen concentration). However, the existing research is not sufficient, and there is a lack of oxygen concentration data collected on the QTP. In this study, through the Second Tibetan Plateau Scientific Expedition and Research and field measurements, the oxygen concentration data and corresponding geographic environmental data were collected at 807 measurement points on the QTP from 2017 to 2022, and the spatiotemporal oxygen concentration patterns were estimated. This work filled the gaps in the measurement and research of oxygen concentrations on the QTP while providing data support for analyses of the influencing factors and spatiotemporal characteristics of oxygen concentrations, which is of great significance for promoting the construction of ecological civilization in the QTP region.

Biomolecule-Driven Two-Factor Authentication Strategy for Access Control of Molecular Devices.

The rise of DNA nanotechnology is promoting the development of molecular security devices and marking an essential change in information security technology, to one that can resist the threats resulting from the increase in computing power, brute force attempts, and quantum computing. However, developing a secure and reliable access control strategy to guarantee the confidentiality of molecular security devices is still a challenge. Here, a biomolecule-driven two-factor authentication strategy for access control of molecular devices is developed. Importantly, the two-factor is realized by applying the specificity and nicking properties of the nicking enzyme and the programmable design of the DNA sequence, endowing it with the characteristic of a one-time password. To demonstrate the feasibility of this strategy, an access control module is designed and integrated to further construct a role-based molecular access control device. By constructing a command library composed of three commands (Ca, Cb, Ca and Cb), the authorized access of three roles in the molecular device is realized, in which the command Ca corresponds to the authorization of role A, Cb corresponds to the authorization of role B, and Ca and Cb corresponds to the authorization of role C. In this way, when users access the device, they not only need the correct factor but also need to apply for role authorization in advance to obtain secret information. This strategy provides a highly robust method for the research on access control of molecular devices and lays the foundation for research on the next generation of information security.

Construction of DNA-based molecular circuits using normally open and normally closed switches driven by lambda exonuclease.

Building synthetic molecular circuits is an important way to realize ion detection, information processing, and molecular computing. However, it is still challenging to implement the NOT logic controlled by a single molecule input in synthetic molecular circuits wherein the presence or absence of the molecule represents the ON or OFF state of the input. Here, based on lambda exonuclease (λ exo), for the first time, we propose the normally open (NO) and normally closed (NC) switching strategy with a unified signal transmission mechanism to build molecular circuits. Specifically, the opposite logic can be output with or without a single signal, and the state of the switch can be adjusted by the addition order and time interval of the upstream signal and switch signal, which endows the switch with time-responsive characteristics. In addition, a time-delay relay with the function of delayed disconnection is developed to realize quantitative control of outputs, which has the potential to meet the automation control need of the system. Finally, digital square and square root circuits are constructed by cascading the NO and NC switches, which demonstrates the versatility of switches. Our design can be extended to time logic and complex digital computing circuits for use in information processing and nanomachines.

Reconfigurable DNA triplex structure for pH responsive logic gates.

The DNA triplex is a special DNA structure often used as a logic gate substrate due to its high stability, programmability, and pH responsiveness. However, multiple triplex structures with different C-G-C+ proportions must be introduced into existing triplex logic gates due to the numerous logic calculations involved. This requirement complicates circuit design and results in many reaction by-products, greatly restricting the construction of large-scale logic circuits. Thus, we designed a new reconfigurable DNA triplex structure (RDTS) and constructed the pH-responsive logic gates through its conformational change that uses two types of logic calculations, 'AND' and 'OR'. The use of these logic calculations necessitates fewer substrates, further enhancing the extensibility of the logic circuit. This result is expected to promote the development of the triplex in molecular computing and facilitate the completion of large-scale computing networks.

Programming DNA Reaction Networks Using Allosteric DNA Hairpins.

The construction of DNA reaction networks with complex functions using various methods has been an important research topic in recent years. Whether the DNA reaction network can perform complex tasks and be recycled directly affects the performance of the reaction network. Therefore, it is very important to design and implement a DNA reaction network capable of multiple tasks and reversible regulation. In this paper, the hairpin allosteric method was used to complete the assembly task of different functional nucleic acids. In addition, information conversion of the network was realized. In this network, multiple hairpins were assembled into nucleic acid structures with different functions to achieve different output information through the cyclic use of trigger strands. A method of single-input dual-output information conversion was proposed. Finally, the network with signal amplification and reversible regulation was constructed. In this study, the reversible regulation of different functional nucleic acids in the same network was realized, which shows the potential of this network in terms of programmability and provides new ideas for constructing complex and multifunctional DNA reaction networks.

A DNA Finite-State Machine Based on the Programmable Allosteric Strategy of DNAzyme.

Living organisms can produce corresponding functions by responding to external and internal stimuli, and this irritability plays a pivotal role in nature. Inspired by such natural temporal responses, the development and design of nanodevices with the ability to process time-related information could facilitate the development of molecular information processing systems. Here, we proposed a DNA finite-state machine that can dynamically respond to sequential stimuli signals. To build this state machine, a programmable allosteric strategy of DNAzyme was developed. This strategy performs the programmable control of DNAzyme conformation using a reconfigurable DNA hairpin. Based on this strategy, we first implemented a finite-state machine with two states. Through the modular design of the strategy, we further realized the finite-state machine with five states. The DNA finite-state machine endows molecular information systems with the ability of reversible logic control and order detection, which can be extended to more complex DNA computing and nanomachines to promote the development of dynamic nanotechnology.

Benefits of subsidence control for coastal flooding in China.

Land subsidence is impacting large populations in coastal Asia via relative sea-level rise (RSLR). Here we assesses these risks and possible response strategies for China, including estimates of present rates of RSLR, flood exposure and risk to 2050. In 2015, each Chinese coastal resident experienced on average RSLR of 11 to 20 mm/yr. This is 3 to 5 times higher than climate-induced SLR, reflecting that people are concentrated in subsiding locations. In 2050, assuming these subsidence rates continue, land area, population and assets exposed to the 100-year coastal flood event is 20%-39%, 17%-37% and 18%-39% higher than assuming climate change alone, respectively. Realistic subsidence control measures can avoid up to two thirds of this additional growth in exposure, with adaptation required to address the residual. This analysis emphasizes subsidence as a RSLR hazard in China that requires a broad-scale policy response, utilizing subsidence control combined with coastal adaptation.

FMG: An observable DNA storage coding method based on frequency matrix game graphs.

Using complex biomolecules for storage is a new carbon-based storage method. For example, DNA has the potential to be a good method for archival long-term data storage. Reasonable and efficient coding is the first and most important step in DNA storage. However, current coding methods, such as altruism algorithm, have the problem of low coding efficiency and high complexity, and coding constraints and sets make it difficult to see the coding results visually. In this study, a new DNA storage coding method based on frequency matrix game graph (FMG) is proposed to generate DNA storage coding satisfying combinatorial constraints. Compared with the randomness of the heuristic algorithm that satisfies the constraints, the coding method based on the FMG is deterministic and can clearly explain the coding process. In addition, the constraints and coding results have observable characteristics and are better than the previously published results for the size of the coding set. For example, when length of the code n = 10, hamming distance d = 4, the results obtained by proposed approach combining chaos game and graph are 24% better than the previous results. The proposed coding scheme successfully constructs high-quality coding sets with less complexity, which effectively promotes the development of carbon-based storage coding.

TripDesign: A DNA Triplex Design Approach Based on Interaction Forces.

A DNA triplex has the advantages of improved nanostructure stability and pH environment responsiveness compared with single-stranded and double-stranded nucleic acids. However, sequence stability and low design efficiency hinder the application of DNA triplexes. Therefore, a DNA triplex design approach (TripDesign) based on interaction forces is proposed. First, we present the stacking force constraint, torsional stress constraint, and G-quadruplex motif constraint and then use an improved memetic algorithm to design triplex sequences under combinatorial constraints. Finally, to quantify the process of triplex formation, we also explore the minimum length of the triplex-forming oligos (TFOs) required to form the triplex and the factors that produce depletion in cyclic pH-jump experiments. The experimental results show that the sequences produced by TripDesign have high stability and reversibility, and the proposed approach achieves efficient and automatic sequence design. In addition, this study characterizes multiple basic parameters of DNA triplex formation and promotes the wider application of DNA triplexes in nanotechnology.

Web-Based Data to Quantify Meteorological and Geographical Effects on Heat Stroke: Case Study in China.

Heat stroke is a serious heat-related health outcome that can eventually lead to death. Due to the poor accessibility of heat stroke data, the large-scale relationship between heat stroke and meteorological factors is still unclear. This work aims to clarify the potential relationship between meteorological variables and heat stroke, and quantify the meteorological threshold that affected the severity of heat stroke. We collected daily heat stroke search index (HSSI) and meteorological data for the period 2013-2020 in 333 Chinese cities to analyze the relationship between meteorological variables and HSSI using correlation analysis and Random forest (RF) model. Temperature and relative humidity (RH) accounted for 62% and 9% of the changes of HSSI, respectively. In China, cases of heat stroke may start to occur when temperature exceeds 36°C and RH exceeds 58%. This threshold was 34.5°C and 79% in the north of China, and 36°C and 48% in the south of China. Compared to RH, the threshold of temperature showed a more evident difference affected by altitude and distance from the ocean, which was 35.5°C in inland cities and 36.5°C in coastal cities; 35.5°C in high-altitude cities and 36°C in low-altitude cities. Our findings provide a possible way to analyze the interaction effect of meteorological variables on heat-related illnesses, and emphasizes the effects of geographical environment. The meteorological threshold quantified in this research can also support policymaker to establish a better meteorological warning system for public health.

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To explore the hydrogen and oxygen stable isotopes and vapor sources of atmospheric precipitation in the loess region of north Shaanxi, we collected 107 samples of precipitation during 2018 to 2020 in the Dingbian County, Shaanxi Province. After measuring δ18O and δ2H of precipitation, we analyzed the isotopic characteristics and vapor sources of precipitation in different seasons. There was obvious seasonal variability in δ18O and δ2H, in that they were more depleted in the wet season (June-September) but more enriched in the dry season (April-May, October-November). In addition, the deuterium excess values were high in the dry season but low in the wet season. The local meteoric water line was regressed as δ2H=7.35δ18O+4.19 (R2=0.96, P<0.01) with slope and intercept lower than that of the global meteoric water line, indicating an impact of evaporation on isotope fractionation. There was temperature effect in the precipitation isotopes for the whole year and for the dry season, while the precipitation isotopes in the wet season were affected by the combined effects of temperature and rainfall amount. The HYSPLIT model showed that the dry season water vapor mainly came from the Atlantic Ocean and the polar Arctic Ocean, while the wet season vapor mainly came from the Indian Ocean and Pacific subject to the Westerly.

Vulnerability to typhoons: A comparison of consequence and driving factors between Typhoon Hato (2017) and Typhoon Mangkhut (2018).

Typhoon disasters have caused casualties, property loss, and other negative impacts to social and economic development. Vulnerability is an important component of typhoon risk. However, little is known about the contributions of vulnerability factors and their interaction effects on typhoon-induced losses at a fine scale. Focusing on the vulnerability measures of Typhoon Hato in 2017 and Typhoon Mangkhut in 2018, this study aims to quantify the contribution and interactive effects of physical and socioeconomic factors on vulnerability based on the GeoDetector method and determine the factors that account for most of the change in vulnerability. The results show that from Typhoon Hato in 2017 to Typhoon Mangkhut in 2018, the vulnerability of the economy and houses decrease on average. Rain intensity and wind intensity are the dominant factors of disaster loss for Typhoon Hato and Typhoon Mangkhut, respectively. Vegetation cover and landform explain vulnerability better than average slope in most instances. For different loss types, the dominant socioeconomic vulnerability factor is different. For both typhoons, emergency transfer has a higher determining power (q) ranking for the population vulnerability, while the percentage of the GDP made up of primary industry have higher q ranking for economic vulnerability. The dominant interaction effects between two vulnerability factors differ depending on the typhoon and loss type but show a nonlinear enhancement effect in most cases. Moreover, changes in the maximum 4-hour accumulated rainfall account for most of the change in vulnerability between Hato and Mangkhut. Overall, the results can be conducive to understanding the complexity of vulnerability to typhoons and provide a reference for possible indicators for vulnerability assessment models, and determining the reasons for changes in vulnerability can be constructive to the formulation of specific policies for disaster prevention and mitigation.

Uncertainties of soil organic carbon stock estimation caused by paleoclimate and human footprint on the Qinghai Plateau.

BACKGROUND: Quantifying the stock of soil organic carbon (SOC) and evaluating its potential impact factors is important to evaluating global climate change. Human disturbances and past climate are known to influence the rates of carbon fixation, soil physiochemical properties, soil microbial diversity and plant functional traits, which ultimately affect the current SOC storage. However, whether and how the paleoclimate and human disturbances affect the distribution of SOC storage on the high-altitude Tibetan Plateau remain largely unknown. Here, we took the Qinghai Plateau, the main component of the Tibetan Plateau, as our study region and applied three machine learning models (random forest, gradient boosting machine and support vector machine) to estimate the spatial and vertical distributions of the SOC stock and then evaluated the effects of the paleoclimate during the Last Glacial Maximum and the mid-Holocene periods as well as the human footprint on SOC stock at 0 to 200 cm depth by synthesizing 827 soil observations and 71 environmental factors. RESULTS: Our results indicate that the vegetation and modern climate are the determinant factors of SOC stocks, while paleoclimate (i.e., paleotemperature and paleoprecipitation) is more important than modern temperature, modern precipitation and the human footprint in shaping current SOC stock distributions. Specifically, the SOC stock was deeply underestimated in near natural ecosystems and overestimated in the strongly human disturbance ecosystems if the model did not consider the paleoclimate. Overall, the total SOC stock of the Qinghai Plateau was underestimated by 4.69%, 12.25% and 6.67% at depths of 0 to 100 cm, 100 to 200 cm and 0 to 200 cm, respectively. In addition, the human footprint had a weak influence on the distributions of the SOC stock. We finally estimated that the total and mean SOC stock at 200 cm depth by including the paleoclimate effects was 11.36 Pg C and 16.31 kg C m-2, respectively, and nearly 40% SOC was distributed in the top 30 cm. CONCLUSION: The paleoclimate is relatively important for the accurate modeling of current SOC stocks. Overall, our study provides a benchmark for predicting SOC stock patterns at depth and emphasizes that terrestrial carbon cycle models should incorporate information on how the paleoclimate has influenced SOC stocks.

Increased probability and severity of compound dry and hot growing seasons over world's major croplands.

Dry and hot extremes are major sources of risk to crop yields, and their impacts are expected to increase under future global warming. The co-occurring dry and hot conditions during crop growing seasons have amplified impacts on crop health that are even larger than the sum of their individual impacts, which may cause crop failure. In this study, we focus on the compound dry and hot growing seasons (hereafter CDHGS) for global wheat, rice, maize and soybean in the period 1951-2020. Total precipitation (TP) and accumulated active temperature (AAT) are used as indicators of overall water stress and heat stress, respectively, at the growing season scale. A copula model is used to construct joint distributions of TP and AAT sequences to investigate the joint behavior of dry and hot conditions during crop growing seasons. Our results indicate that after 1980, the growing seasons of the four crops become drier and more rapidly hotter across the globe, the probability of extreme CDHGS (P(TP ≤ TP25,AAT > AAT75)) increases in more than 80% of global croplands, the severity of CDHGS increases in more than 83% of global croplands, especially in Europe, Central Africa and eastern China. This study provides a global dimension analysis on the changes in compound dry and hot stresses within crops growing seasons in the context of global warming, offering helpful techniques to study the interaction between multi-hazards that occur during crop growth processes, which can effectively contribute to guiding the decision-making processes related to risk reduction and agricultural practices.

Precise control of embolic stroke with magnetized red blood cells in mice.

Precise embolism control in immature brains can facilitate mechanistic studies of brain damage and repair after perinatal arterial ischemic stroke (PAIS), but it remains a technical challenge. Microhemorrhagic transformation is observed in one-third of infant patients who have suffered PAIS, but the underlying mechanism remains elusive. Building on an established approach that uses magnetic nanoparticles to induce PAIS, we develop a more advanced approach that utilizes magnetized erythrocytes to precisely manipulate de novo and in situ embolus formation and reperfusion in perinatal rodent brains. This approach grants spatiotemporal control of embolic stroke without any transarterial delivery of pre-formed emboli. Transmission electron microscopy revealed that erythrocytes rather than nanoparticles are the main material obstructing the vessels. Both approaches can induce microbleeds as an age-dependent complication; this complication can be prevented by microglia and macrophage depletion. Thus, this study provides an animal model mimicking perinatal embolic stroke and implies a potential therapeutic strategy for the treatment of perinatal stroke.

Reducing livestock snow disaster risk in the Qinghai-Tibetan Plateau due to warming and socioeconomic development.

Global warming can have positive or negative impacts on society depending on sectors and changes in climate impact drivers, resulting in opportunities or risks. The same holds true for social-economic changes. However, past research has mostly focused on assessing risks, leaving potential opportunities under-addressed. Here, we simulated the impact of climate change and socioeconomic development on livestock snow disasters over the Qinghai-Tibetan Plateau during 1986-2100, by integrating the drivers of climate and socioeconomic changes via an event-based disaster risk assessment model. Model results show climate change and socioeconomic development contributes about equally to reducing livestock loss in snow disasters by 4% yr-1 up to 2100 under representative concentration pathway 8.5 and shared-socioeconomic pathway 5. The marginal benefit from climate change was projected to be a 43.2% reduction in annual average loss per degree kelvin warming, and that from socioeconomic development was a 12.4% reduction per 100% increase in gross domestic production. In a 2 °C warmer world, the annual average loss could be 91% smaller compared with the baseline period (1986-2005). Limiting global warming to 1.5 °C instead of 2 °C would reduce the benefit by 5%, requiring a 135% increase in the marginal benefits of prevention capacity to offset the reduction.